Introduction
Senescence – the deterioration of health and performance in old age –
occurs in nearly all species (Nussey et al. , 2013). However,
within species there can be considerable individual variation in the
onset and rate of senescence (e.g. Lemaître et al. , 2013). Thus,
individuals may be biologically older or younger than expected for their
chronological age. Measuring ‘biological age’ (Baker and Sprott, 1988)
is valuable, not only in regards to organismal health but also in terms
of understanding fundamental concepts in ecology and evolution e.g.
trade-offs in life-history strategies, or the impact of different
environmental stressors (Stearns, 2008; Lemaître et al. , 2015).
Telomeres are repetitive nucleotide sequences at the ends of
chromosomes, which protect the functional integrity of the genome. Due
to the ‘end replication problem’ (Watson, 1972), telomeres shorten with
each cell division, until a critical length is reached where cells can
no longer divide (Olovnikov, 1996; Campisi, 2003) Telomeres also shorten
when exposed to sources of cellular damage, such as reactive oxygen
species (Von Zglinicki, 2002; Reichert and Stier, 2017). Both the number
of cell-divisions and cell damage load are cumulative (i.e.
age-dependent) but also variable in rate. Telomere length shortens with
increasing age in a broad range of taxa (Barrett et al. , 2013;
Bendix et al. , 2014; Stier et al. , 2015) but see Fairlieet al. (2016).
There is considerable empirical evidence to support the idea of telomere
length being a marker of biological age. Accelerated telomere shortening
occurs as an outcome of life-history or environmental conditions
associated with increased cellular division and reactive oxygen species
production, including developmental growth (Salomons et al. ,
2009; Monaghan and Ozanne, 2018), early-life adversity (Boonekampet al. , 2014; Watson, Bolton and Monaghan, 2015) and reproductive
effort (Reichert et al. , 2014; Sudyka et al. , 2014).
Shorter telomeres and/or higher attrition rates are associated with
increased mortality risk (e.g. Haussmann, Winkler and Vleck, 2005; Veraet al. , 2012; Fairlie et al. , 2016; Barret et al .,
2013) and ‘faster’ life histories (Haussmann et al. , 2003;
Sudyka, Arct, et al. , 2019). Therefore, telomere length has been
proposed as a valuable biomarker linking past life-history costs to
future performance (Young, 2018).
Over the last decade there has been a rapid expansion in studies
investigating the causes and consequences of telomere dynamics across a
wide range of taxa and environmental situations. However, our growing
awareness of the complexity of telomere dynamics raises important
questions on how we interpret telomeres as a biomarker. Longitudinal
studies in humans and some wild vertebrates have shown that
within-individual changes in telomere length are highly variable and
bidirectional (Svenson et al. , 2011; Fairlie et al. , 2016;
Hoelzl et al. , 2016; Spurgin et al. , 2017; van Lieshoutet al. , 2019). Until recently, observations of telomere
lengthening were often attributed to measurement error between samples
collected too close in time – relative to the rate of telomere loss –
to detect telomere shortening (Chen et al. , 2011; Steenstrupet al. , 2013). However, it is now recognised that the degree or
frequency of observed telomere lengthening is often greater than that
expected from measurement error alone (Bateson and Nettle, 2017; Spurginet al. , 2017; van Lieshout et al. , 2019).
Telomere lengthening within the same individual may be observed for a
variety of reasons. First, the enzyme telomerase can restore lost
telomere length (Blackburn et al. , 1989). Since telomeres shorten
during cell division, telomerase remains active in cell lineages
requiring greater proliferation potential, such as haematopoietic stem
cells (Morrison et al. , 1996; Haussmann et al. , 2007).
Telomeres can also lengthen via alternative mechanisms, independent of
telomerase (see Cesare and Reddel, 2010 for a discussion). Importantly,
telomere measurements may increase in subsequent assays due to changes
in clonal cell composition, i.e. an increase in long-telomere cells
relative to short-telomere cells. All the mechanisms explained above are
relevant to the telomere dynamics of blood, the tissue most often
utilised for ecological and evolutionary studies on vertebrates (Nusseyet al. , 2014). Furthermore, in mammals the proportions of
circulating leucocyte cell types (with differing telomere lengths; Weng,
2012) can also change dramatically within an individual, for example in
response to infection, resulting in apparent changes in overall telomere
length (Beirne et al. , 2014). In birds and reptiles,
blood-derived assays of telomere length overwhelmingly stem from
nucleated erythrocytes (Stier et al. , 2015), and telomerase
activation or turnover in haematopoietic cell lines could, in theory,
create heterogeneity in measured telomere length.
The importance of (apparent) telomere lengthening in wild populations
remains uncertain. Since telomere attrition occurs as a consequence of
life-history or environmental stress costs, telomere lengthening may
reflect investment in self-maintenance when those costs are alleviated.
For example, wild edible dormice (Glis glis ) that receive
supplementary food showed lengthened telomeres (Hoelzl et al. ,
2016). In other wild species, changes in telomere length reflected
temporal differences in environmental conditions, with lengthening
coinciding with more favourable environments (e.g. Mizutani et
al. , 2013; Foley et al. , 2020). Telomere dynamics can also
reflect changes in parasitic pressure. For example, infection with
malaria has been associated with telomere attrition in wild and captive
birds (Asghar et al. , 2016), but the clearing of infections in
humans can result in lengthening (Asghar et al. , 2018). The
ability of telomeres to both shorten and lengthen, rather than being an
irreversible one-way ratchet, suggests that we may have to rethink our
interpretation of telomere dynamics. Instead of reflecting the
accumulation of all past stressors and growth, telomere length may be
more of a short-term marker, reflecting an individual’s current
condition consequent on the challenges and trade-offs faced by an
individual. However, in contrast to telomere shortening, the
circumstances under which telomere lengthening occurs in natural
populations remain poorly understood.
Given the fitness costs associated with shorter, or more rapidly
shortening, telomeres (see above), one might expect improved fitness to
be associated with telomere lengthening. Recent reviews argue that
telomere dynamics are a non-causal biomarker of accumulated cellular
damage – such as that occurring from oxidative stress – that
subsequently impacts fitness (Simons, 2015; Young, 2018). However, there
is evidence that active restoration of telomere length can impact
organismal performance. First, telomere lengthening could reduce the
frequency of critically short telomeres – thought to directly
contribute to organismal ageing by inducing cellular senescence and
apoptosis (Vera et al. , 2012; Van Deursen, 2014). Secondly,
telomerase has restorative effects on cells (Cong and Shay, 2008;
Criscuolo et al. , 2018). Both telomerase activity and telomere
lengthening are associated with tissue regeneration (Anchelin et
al. , 2011; Reichert, Bize, et al. , 2014) and telomerase
overexpression in mice is beneficial to a range of health parameters
(Bernardes de Jesus et al. , 2012; Simons, 2015). Conversely,
active telomere lengthening could also have negative effects, such as
proliferating cancers (Shay and Wright, 2011) or by diverting energy
from competing traits (Young, 2018). Nonetheless, telomere lengthening
has the potential to be associated with organismal performance, and this
impact is not dependent on telomere length playing a causal role in
organismal ageing.
In this study, we aim to determine when and why telomere lengthening
occurs, and assess its association with survival, in a wild population
of the facultative cooperatively breeding Seychelles warbler
(Acrocephalus sechellensis ). Previous studies on this population
have shown that telomeres shorten with age, and individuals with shorter
telomeres are less likely to survive to the following year (Barrettet al. , 2013). Furthermore, telomere shortening is associated
with various stresses in this species, including inbreeding (Bebbingtonet al. , 2016), intra-specific antagonistic interactions
(Bebbington et al. , 2017) and parental care (Hammers et
al. , 2019). However, telomere lengthening is often observed between
successive samples taken from the same adult individual, and is greater
than that expected from measurement error alone (Spurgin et al. ,
2018). We predict that telomere lengthening occurs in individuals that
experience reduced stress. Specifically, we predict that, for adults,
telomere lengthening will be associated with reduced reproductive effort
(less breeding, higher food availability and the presence of helpers)
and an absence of malaria (the only known parasite in the population).
We expect this relationship to be sex-specific, given that reproductive
investments differ between sexes in this species (Hammers et al. ,
2019; van Boheemen et al. , 2019). Furthermore, we tested whether
increased survival is associated with telomere lengthening.